Is CHEK2 p.Val211= (c.633T>C) pathogenic?

CHEK2 p.Val211= (c.633T>C) is classified Benign/Likely benign in CHEK2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-11-25). Ultra-rare (popmax 0.0292%, sas); Associated with hereditary nonpolyposis colon cancer.

What condition is associated with CHEK2 p.Val211= (c.633T>C)?

CHEK2 p.Val211= (c.633T>C) is associated with hereditary nonpolyposis colon cancer, hereditary neoplastic syndrome, hereditary breast carcinoma (ClinVar).

How common is CHEK2 p.Val211= (c.633T>C) in the general population?

CHEK2 p.Val211= (c.633T>C) is ultra-rare (popmax 0.0292%, sas) (gnomAD).

CHEK2 p.Val211=

c.633T>C · rs1555924460 · VCV630923

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0292%, sas)

Conditions

hereditary nonpolyposis colon cancer

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.1	GERP -1.3, phastCons 1
Overall
CADD	11.81	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0292% South Asian · 26/89,044 alleles

Filtering AF 0.0205% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0175%

Overall 0.0018% 26/1,446,456 alleles · ultra-rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CHEK2
Protein: p.Val211=
Coding: c.633T>C
MANE Select: NM_007194
dbSNP: rs1555924460
Type: single nucleotide variant
Location: chr22:28719445 (GRCh38)
Gene constraint: LOEUF 1.399 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.64 · 38 PDB
Residue 211: an α-helix

Full CHEK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary nonpolyposis colon cancer — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome hereditary breast carcinoma

Similar variants

CHEK2 p.Val211Phe Uncertain significance ★★ ⚠ same residue
CHEK2 c.1008+1G>A Likely pathogenic ★★ same condition
CHEK2 c.1008+1G>T Likely pathogenic ★★ same condition
CHEK2 c.1008+2T>A Likely pathogenic ★★ same condition
CHEK2 c.1008+2T>G Likely pathogenic ★★ same condition
CHEK2 c.1009-1G>A Likely pathogenic ★★ same condition
CHEK2 c.1009-2A>C Likely pathogenic ★★ same condition
CHEK2 c.1009-2A>G Likely pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/chek2-p-val211 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown